The infectious cycle of the human adenovirus (Ad), a DNA tumor virus, complex and poorly understood. Nevertheless, some insight into this process may be gained by studying the Ad infectious process in cell lines that originate from different species. For example, human cells are known to support a complete, productive infection (i.e., are permissive) by Ad type 12, while hamster cells completely block production of the same virus (i.e., are nonpermissive). In contrast, both human and hamster cells are permissive to infection by a related virus, Ad type 2. The aim of this research is to use differences in permissivity as tools for investigating the process of viral infection. The work described in this proposal is focused on two initial and fundamental aspects of this research topic. First, the synthesis of Ad 12 early proteins in human (permissive) and hamster (nonpermissive) cell lines will be compared. Since Ad 12 infection is blocked at the DNA replication stage in hamster cells, it seems likely that there will be differences in the expression of Ad 12 early proteins, whose synthesis is a necessary precondition to viral DNA replication. These differences will be explored biochemically and genetically. Biochemically, Ad 12 early proteins will be directly identified in infected hamster cells by immunoprecipitation with specific antibodies. Genetically, Ad 12 will be tested for its ability to complement, by coinfection of hamster cells, Ad 2 mutants that are defective for specific early proteins. The results of these studies should provide insight regarding those specific viral gene loci that are involved in the permissive and nonpermissive cell-virus interactions.